DESCRIPTION (provided by investigator): Further research is needed to inform new policy initiatives to reduce the burden of developmental impairment in children. We propose to extend and enrich a molecular epidemiologic prospective cohort study launched in 2000 to assess the longer-term neurobehavioral effects of prenatal exposure to PAHs in children. PAHs are ubiquitous in urban air from combustion of fossil fuel. The study population is unique, comprising more than 400 Caucasian mothers and children residing in Krakow, Poland who have been followed since pregnancy. Follow-up of the cohort is required because we have observed significant adverse effects of prenatal exposures to PAHs on child development among children followed through age five. We have also observed marked inter-individual variation in response to the same levels of exposure, indicating susceptibility due to genetic or nutritional factors. Because the retention rate in this cohort has been high, we are readily able to extend the study through school age (age nine), allowing us to diagnose neurodevelopmental problems that may ultimately impact learning and academic performance. Our primary aim is to determine the effect of prenatal exposures to airborne PAHs on neurobehavioral development from birth through age nine years of age, after controlling for the effects of postnatal PAH exposure, known determinants of child development, and potential confounders. Our secondary aims will be to explore the modifying roles of a) genetic polymorphisms in metabolic activation and detoxification genes and b) lipid- soluble micronutrient concentrations in cord and maternal blood on the associations between prenatal PAH exposure and neurobehavioral development through age nine years. We will also compare results from this cohort study in Caucasians with those from African Americans and Dominicans in our parallel study being conducted in New York City. There are few such comprehensive cohort studies beginning in pregnancy that can provide needed policy-relevant information on neurodevelopmental risks from common urban pollutants. We anticipate that this study will provide a sound evidence-base not only on air pollution exposures, but also on susceptibility factors which may contribute to the risk of neurodevelopmental disorders. PUBLIC HEALTH RELEVANCE: Rates of developmental disorders have increased in children over the past decade and prenatal exposure to environmental contaminants such as polycyclic aromatic hydrocarbons (PAHs) has been implicated. The results of this cohort study will address a major gap in knowledge. The exposures we are studying are not unique to Poland but are ubiquitous worldwide;our results will thus be generalizable to other geographic and ethnic populations.